The mu opiate receptor (OR) has been identified as the principal brain receptor site best correlated with the rewarding and euphoric properties of opiate drugs. This year investigators in this Branch have continued with vastly-reduced work with mu receptor knockout mice and the human OPRM1 locus due to personnel attenuation. Work on mu knockout mice during this year continued to document modest effects of mu knockout on several intersting features, including the relative robustness of the mu knockout effects to genetic background and effects of mu deletion on reward phenotypes from more and more drugs. During this year these investigators continued to attempt to localize the association genome scanning signals associatied with addiction vulnerability in several different human ganome scanning samples, identifying association with the adjacent regulator of G signaling (RGS17) gene that could contribute to assocations with markers lying in the chromosomal vicinity of OPRM1 that have been identified intermittently in human samples.